Of the many examples of post-translational processing of precursor proteins, proteolysis remains an important element in generating structural and functional diversity. Most growth factors are synthesized as soluble precursor proteins. These precursors lack specific biological activities and are primarily confined to Golgi or lysosomal compartments within the cell. Proteolytic cleavage of these precursors generates the mature growth factors which are then secreted from the cell. Specialized eukaryotic proteinases appear to be responsible for the proteolytic processing of prohormones, neuropeptide precursors, and other growth factor precursors. These proteinases are remarkably specific and cleave at particular sequences of basic residues. Subsequent to cleavage by these proteinases, a particular pathway further processes the polypeptides to generate alpha-carboxamidated peptides. Two assays have been developed for the alpha-carboxamidated peptides and their immediate precursors, the glycine-extended forms. Using these assays, tissue extracts are being screened for polypeptides arising from proteolysis of growth factor precursors. Another pathway of processing, cleavage at multibasic sites, is being explored in cultured cells using a fluorogenic substrate of the putative proteinase responsible for cleavage of several growth factors, including transforming growth factor beta.